Transforming growth factors type B (TGF-beta s) are proteins forming 25 kD disulfide-linked homodimers which act to control the proliferation of a variety of both normal and transformed cell types. In addition, TGF-beta s have been shown to stimulate wound healing, and to act as potent immunosuppressive agents. Recently, we identified a new form of TGF-beta, which we termed TGF-beta 3. Sequence determination of three overlapping cDNA clones revealed an extensive homology of TGF-beta 3 with TGF-beta 1 and beta 2. The purpose of this Phase I research proposal is to express TGF- beta 3 cDNA in mammalian cell lines. Conditioned media of cells expressing high levels of TGF-beta 3 will be tested for their ability to modulate the growth of cells in both monolayer and soft agar. In Phase II, we propose to carry out a detailed analysis of the structure, function and potential therapeutic uses of recombinant TGF-beta 3.